1. Technical Field
This document relates to methods and materials involved in assessing samples for enzyme-nucleic acid complexes. For example, this document relates to methods and materials for using antibodies to determine the presence, absence, or amount of enzyme-nucleic acid complexes (e.g., human topoisomerase I-DNA complexes) in a sample (e.g., a biological sample such as a tissue biopsy).
2. Background Information
Topoisomerase I (topo I) is an abundant (up to 1,000,000 copies/cell) enzyme that relaxes torsional strain in DNA during the course of a variety of nuclear processes (Pommier, Nat. Rev. Cancer, 6:789-802 (2006); Wang, Nat. Rev. Mol. Cell. Biol., 3:430-440 (2002); and Champoux, Annual Review of Biochemistry, 70:369-413 (2001)). Studies have demonstrated roles for topo I in replication, transcription, and viral integration. Additional studies have demonstrated that topo I is the target for a class of widely utilized anticancer drugs, the camptothecins (Eng et al., Mol. Pharmacol., 34:755-760 (1988); and Bjornsti et al., Cancer Res., 49:6318-6323 (1989)). In particular, irinotecan is approved for the treatment of colorectal cancer alone and in combination with 5-fluorouracil. This agent also has activity in non-small cell lung cancer, pancreatic cancer, and breast cancer. Topotecan (TPT), another camptothecin analogue, is approved for the treatment of ovarian and small cell lung cancer. In addition, this agent is currently being investigated for its potential activity in acute myelogenous leukemia. Additional novel topo I poisons continue to be developed and investigated (Pommier, Nat. Rev. Cancer, 6:789-802 (2006); Pommier and Cushman, Mol. Canc. Ther., 8:1008-1014 (2009); and Mow and Kaufmann, Use of camptothecins in the treatment of leukemia and related disorders; In Adams V R, Burke T G (eds): Camptothecins in Cancer Therapy. Totowa, N.J., Humana Press, Inc., 2005, pp 421-450).